Opacity factor activity and epithelial cell binding by the serum opacity factor protein of Streptococcus pyogenes are functionally discrete

Gillen, Christine M., Courtney, Harry S., Schulze, Kai, Rohde, Manfred, Wilson, Mark R., Timmer, Anjulli M., Guzman, Carlos A., Nizet, Victor, Chhatwal, G. s. and Walker, Mark J. (2008) Opacity factor activity and epithelial cell binding by the serum opacity factor protein of Streptococcus pyogenes are functionally discrete. Journal of Biological Chemistry, 283 10: 6359-6366. doi:10.1074/jbc.M706739200

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Author Gillen, Christine M.
Courtney, Harry S.
Schulze, Kai
Rohde, Manfred
Wilson, Mark R.
Timmer, Anjulli M.
Guzman, Carlos A.
Nizet, Victor
Chhatwal, G. s.
Walker, Mark J.
Title Opacity factor activity and epithelial cell binding by the serum opacity factor protein of Streptococcus pyogenes are functionally discrete
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2008-03-01
Sub-type Article (original research)
DOI 10.1074/jbc.M706739200
Open Access Status File (Publisher version)
Volume 283
Issue 10
Start page 6359
End page 6366
Total pages 8
Place of publication Bethseda, MD, United States
Publisher American society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Serum opacity factor (SOF) is a unique multifunctional virulence determinant expressed at the surface of Streptococcus pyogenes and has been shown to elicit protective immunity against GAS infection in a murine challenge model. SOF consists of two distinct domains with different binding capacities: an N-terminal domain that binds apolipoprotein AI and a C-terminal repeat domain that binds fibronectin and fibrinogen. The capacity of SOF to opacify serum by disrupting the structure of high density lipoproteins may preclude its use as a vaccine antigen in humans. This study generated mutant forms of recombinant SOF with reduced (100-fold) or abrogated opacity factor (OF) activity, for use as vaccine antigens. However, alterations introduced into the N-terminal SOF peptide (SOFΔFn) by mutagenesis to abrogate OF activity, abolish the capacity of SOF to protect against lethal systemic S. pyogenes challenge in a murine model. Mutant forms of purified SOFΔFn peptide were also used to assess the contribution of OF activity to the pathogenic processes of cell adhesion and cell invasion. Using latex beads coated with full-length SOF, SOFΔFn peptide, or a peptide encompassing the C-terminal repeats (FnBD), we demonstrate that adhesion to HEp-2 cells is mediated by both SOFΔFn and FnBD. The HEp-2 cell binding displayed by the N-terminal SOFΔFn peptide is independent of OF activity.Wedemonstrate that while the N terminus of SOF does not directly mediate intracellular uptake by epithelial cells, this domain enhances epithelial cell uptake mediated by full-length SOF, in comparison to the FnBD alone.
© 2008 by American Society for Biochemistry and Molecular Biology
Keyword Group-A Streptococci
High-Density-Lipoprotein
Fibronectin-Binding
Surface Protein
M1 Protein
Intranasal Immunization
Intracellular Invasion
Conformational Epitope
Northern-Territory
Lipoteichoic Acid
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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